Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis

Ray, A and Loghinov, I and Ravindranath, V and Barth, AL (2024) Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis. In: iScience, 27 (9).

Preview	PDF iSci_2024(2).pdf - Published Version Download (6MB) | Preview
	Archive (ZIP) iSci_Vol_27_Iss_9_Sup_2024.zip - Published Supplemental Material Download (35MB)

Abstract

The limited success of plaque-reducing therapies in Alzheimer's disease suggests that early treatment might be more effective in delaying or reversing memory impairments. Toward this end, it is important to establish the progression of synaptic and circuit changes before onset of plaques or cognitive deficits. Here, we used quantitative, fluorescence-based methods for synapse detection in CA1 pyramidal neurons to investigate the interaction between abnormal circuit activity, measured by Fos-immunoreactivity, and synapse reorganization in mouse models of amyloidosis. Using a genetically encoded, fluorescently labeled synaptic marker in juvenile mice (prior to sexual maturity), we find both synapse gain and loss depending on dendritic location. This progresses to broad synapse loss in aged mice. Elevated hippocampal activity in both CA3 and CA1 was present at weaning and preceded this reorganization. Thus, Aβ overproduction may initiate abnormal activity and subsequent input-specific synapse plasticity. These findings indicate that sustained amyloidosis drives heterogeneous and progressive circuit-wide abnormalities. © 2024 The Authors

Item Type:	Journal Article
Publication:	iScience
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to authors.
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience Autonomous Societies / Centres > Centre for Brain Research
Date Deposited:	18 Nov 2024 17:28
Last Modified:	18 Nov 2024 17:28
URI:	http://eprints.iisc.ac.in/id/eprint/86832

Actions (login required)

View Item